Breast Cancer Patients and Gene Mutations

Gene mutations found in 22% of African American breast cancer patients

CHICAGO – BROCA, a genetic screening panel that combines BRCA1 and BRCA2 testing with screening for all 18 known breast cancer genes, detected at least one loss of function mutation in 56 of 249 unrelated African American women with breast cancer.

African American women are disproportionately affected by early-onset and triple-negative breast cancers, possibly because of a higher frequency of inherited mutations in DNA repair pathways. The finding of abnormalities in 22% of these women represents the first comprehensive screen of all known breast cancer susceptibility genes using next-generation sequencing in African American women, according to Dr. Jane E. Churpek, who reported the results at the annual meeting of the American Society of Clinical Oncology.

These high carrier frequencies suggest the importance of screening for all gene mutations in African American breast cancer patients who are diagnosed at a young age, have a family history, or have triple-negative breast cancer. The results should be used to encourage testing of at-risk family members to identify those who would benefit from lifesaving interventions, said Dr. Churpek of the University of Chicago.

In the 249-patient study, inherited damaging mutations were seen in 44 of 144 patients with a family history and in 12 of 145 women without a family history of breast and ovarian cancer. Of the 67 women who had triple-negative disease, 20 (30%) had mutations; in the 146 women under age 45, 67 (27%) had mutations.

"Even in the absence of triple-negative disease and family history, there are patients with gene mutations," she said.

While the majority of the 56 women with mutations were positive for BRCA1 (26 patients) or BRCA2 (20 patients), other inherited mutations detected in the BROCA panel were found in 10 patients. Those mutations included CHEK2 (n = 3), PALB2 (n = 3), ATM (n = 5), and PTEN (n = 1), she reported. The study population consisted of women who were treated at the University of Chicago cancer risk and breast cancer clinics.

Having an all-encompassing test like BROCA would allow women to undergo a single test, Dr. Churpek said. Further, advances in technology via targeted genomic capture and next generation sequencing allow this test to be performed inexpensively using 3 mcg of peripheral blood. The current clinical approach to testing requires BRCA1 and BRCA2 testing (BRACAnalysis, Myriad) and possible further testing via a genetic panel, which can be expensive and sometimes difficult to get covered by payers, Dr. Churpek said.

She said there are no plans to market the BROCA test, however. Myriad Genetics holds the U.S. patent on the BRCA genes in the context of cancer diagnostics until 2015. The U.S. Supreme Court is considering the legal issues surrounding the gene patent in the case of Association for Molecular Pathology v. Myriad Genetics. Oral arguments in the case were heard in April, and a decision from the court is expected before July.

Dr. Churpek had no financial disclosures.

Source: By: MARY JO M. DALES, Ob.Gyn. News Digital Network

Dose Impacts African Americans

Genetic Variations Impact Warfarin Doses For African Americans

A common genetic variation that can impact the therapeutic dose of the blood-thinning drug warfarin among African Americans has been found, according to a new report in The Lancet.

The finding revealed that people of African ancestry who have the rs12777823 variant require a notably lower dose of warfarin to achieve all the advantages, compared to those without this single-nucleotide polymorphism (SNP).

Julie Johnson from the University of Florida and lead researcher explained:

"Adding this genetic marker - found in more than 40% of African American patients in the study - to standard dosing algorithms improved the predictability of warfarin dosing by 21% in these individuals, which has the potential to increase the safety and effectiveness of this notoriously hard to dose drug."

Warfarin is used to prevent blood clots in patients who experienceatrial fibrillation, have a history of blood clots, or after major surgery. It is one of the most prescribed drugs around the world, adding up to around 35 million prescriptions in the USA in 2011.

Dosage requirements range widely between people, making it hard to get the dose correct. Additionally, warfarin contributes to a third of hospitalizations for adverse drug reactions in people over 65 years of age in the USA.

Previous research has revealed that two genes, VKORC1 and CYP2CP, can account for about 30% of the difference in warfarin response in people of Asian and European descent. 

However, these genetic markers are less predictive of dosing regimens in African Americans.

In order to pinpoint additional genetic factors that control warfarin dose requirements in African Americans, the investigators examined health information and DNA samples from 533 African-American adults on stable doses of warfarin from the International Warfarin Pharmacogenetics Consortium (IWPC) sites and the University of Alabama at Birmingham.

After checking through a range of genomes, the researchers found that the strongest signals were clustered around the well-known VKORC1 and also found a significant link between the rs12777823 variant on chromosome 10 and warfarin dose. This result was verified in an independent cohort of 432 additional African American patients.

The outcomes suggest that African Americans who carry one or two copies of this polymorphism need a dose decrease of approximately 7-9 mg less per week compared to other patients.

Mark Alberts, from UTSW Medical Center in Texas, commented on the study saying:

"Use of genetic backgrounds to help to guide warfarin dosing has been advocated for several years by the US Food and Drug Administration... However, the practical aspects (and limitations) have not been fully appreciated. Genetic testing has several challenges: it is not widely available in some areas; it is costly; and clinicians often can identify the correct dose before test results are available. If these problems were corrected, the actual use of such tests might increase substantially."

Source: Medical News Today/Written by Kelly Fitzgerald 

Gene Identified in Blacks

Gene linked to higher Alzheimer's risk in blacks

A new gene has been identified that doubles an African American's risks for getting Alzheimer's disease, suggesting a new target to treat in the most common form of dementia, according to a report.

(Photo: Comstock Images)

Story Highlights

• This is the largest genome-wide study for Alzheimer's in African Americans
• The ABCA7 gene is involved in the production of cholesterol and lipids
• Genetic underpinnings for the disease may vary among populations

A new gene mutation has been identified that nearly doubles African Americans' risk for getting Alzheimer's disease, according to a large, government-funded report.

The mutation in the gene ABCA7 is not the first linked to the disease but it is a major breakthrough in research, suggesting there could be multiple causes of Alzheimer's and therefore ways to treat the most common form of dementia, says the report, published Tuesday in the Journal of the American Medical Association.

There is no effective way to prevent, cure or delay Alzheimer's, a neurodegenerative illness that robs people of memory and other cognitive and emotional functions. The predominant late-onset form of Alzheimer's occurs after age 65 and is more common in blacks than whites. The study involved almost 6,000 black volunteers who had genetic testing; approximately 2,000 were diagnosed with probable Alzheimer's and 4,000 were cognitively normal.

"The first thing this tells us is there are probably many different ways to get Alzheimer's,'' says the study's senior author, Richard Mayeux, chair of the department of neurology at Columbia University Medical Center, New York. "It might be like some forms of cancer where the type of cancer you have dictates the type of treatment you receive."

The ABCA7 gene is involved in producing cholesterol and lipids, suggesting they may be a more important pathway in Alzheimer's disease in blacks than in whites, the authors say. High cholesterol and lipid levels can lead to vascular disease, heart attacks and strokes and are more common in blacks.

Treatments that lower cholesterol and lipids may potentially be an effective way to reduce or delay Alzheimer's in patients with the gene variant, Mayeux says.

A variant, or mutation, is an abnormal change in the sequence of the chemicals inside a gene. Whites with the ABCA7 mutation are also at increased risk, but not as significantly as blacks, he adds.
Several gene mutations have been linked with increased Alzheimer's risk; the most significant in both whites and blacks has been APOE-e4, says Mayeux. But the study authors say that both ABCA7 and APOE-e4 are "major genetic risk factors" in blacks.

"This is a major finding because it shows that blacks have an additional risk factor compared to whites,'' says Neil Buckholtz, director of neuroscience at the National Institute on Aging, a branch of the National Institutes of Health. NIH funded the study. "It's a highly significant risk that doesn't exist in other populations. In order to find interventions, we need to explore all the various risks."

APOE-e4 is associated with an increased number of amyloid plaques in the brain, which form into toxic clumps that destroy brain cells. Other processes, such as inflammation and insulin receptivity, are also being explored as possible contributors. ABCA7 also transports a precursor of amyloid plaques.

"We're definitely finding that there are layers to the disease,'' says Heather Snyder, a researcher for the Alzheimer's Association. She was not involved in this study. "We need to do more research to find out what these targets are doing in the brain so we can find treatments and ways of delaying the disease from starting."

About 5 million adults in the USA have Alzheimer's, and numbers are expected to more than triple by 2050 and cost $1.1 trillion a year annually. About a third of the people with late-onset Alzheimer's are 80 and older. It is the only disease among the top 10 killers that has no effective treatments.

Snyder says the Alzheimer's Association does not recommend people get genetic testing because the links aren't clearly established and some people who have the gene variants do not get the disease.
Source: Janice Lloyd, USA Today 

Prostate Cancer among Black Men

Baldness, prostate cancer linked among black men

Baldness seems to confer a significantly increased risk of prostate cancer upon black men – particularly if they lose their hair before age 60 years.

Different patterns of baldness were also related to different grades of cancer, Charnita Zeigler-Johnson, Ph.D., and her colleagues reported in the March 26 online issue of Cancer, Epidemiology, Biomarkers, and Prevention (Canc. Ep. Biomark. Prev. 2013;22: 589-96).Those with frontal baldness were more than twice as likely to have high-grade and high-stage disease at diagnosis than were those with other hair loss patterns, wrote Dr. Zeigler-Johnson of the University of Pennsylvania, Philadelphia, and her coauthors.

The researchers’ case-control study comprised 318 black patients with prostate cancer and 219 black controls. The subjects were matched for age and other baseline characteristics. However, patients were significantly older than controls (60 vs. 57 years), and more likely to report a family history of prostate cancer (36% vs. 27%). Any form of baldness occurred in significantly more patients than in controls (20% vs.13%).

When the investigators conducted a multivariate analysis, they found a number of significant associations between the cancer and hair loss. Compared with those without hair loss, men with any form of baldness were 69% more likely to have prostate cancer. Frontal baldness was associated with more than a doubling in the risk of both high-stage and high-grade disease (odds ratio, 2.61 and 2.20, respectively).

Men with vertex balding who developed prostate cancer were significantly more likely to present with a low-grade tumor (OR, 1.45).

When the authors broke the groups down by age, they found no significant associations with disease severity among men older than 60 years. Instead, these risks were concentrated in men younger than 60 years. Among these, baldness increased the risk of high-stage cancer by more than three times (OR, 3.43) and more than doubled the risk high-grade disease (OR, 2.33). Frontal baldness was a particularly ominous risk factor for younger men, being associated with more than six times the risk of high-stage disease and more than four times the risk of high-grade disease (OR, 6.51 and 4.23, respectively).

There were also significant relationships observed between baldness and prostate specific antigen levels at diagnosis among younger men. Any baldness was associated with a tripling in the risk of a high PSA (10 ng/mL or more) at diagnosis. The association was stronger for men with frontal-only baldness (OR, 5.29).

The authors speculated that the elevated risks are related to genetically determined androgen metabolism. "There are differences in the prevalence of genotypes that metabolize testosterone and influence dihydrotestosterone (DHT) levels," they wrote. "High DHT levels have been associated with both early pattern baldness and prostate cancer processes, including increases in PSA levels."

In particular, they noted, four genes known to be associated with early-onset baldness are also involved in pathways of androgen metabolism, hair development, and age-related neurodegenerative disease.

"Given the high prevalence of prostate cancer in African Americans, early-onset baldness may be a particularly relevant indicator of risk that deserves attention in future studies as we seek to advance our knowledge about high-risk populations."

None of the authors had any financial disclosures. The work was funded by the Department of Defense and the Public Health Service.

Source: International Medical News Group, LLC /msullivan@frontlinemedcom.com/ Oncology Practice

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Fast-Food Intake and Race

Another health study that does not include Multiracial people. 

Fast-Food Intake Highest Among Young, Black, and Obese Adults

From 2007 to 2010, the average American adult obtained just over a tenth of his or her daily calories from restaurant fast food or pizza, according to a cross-sectional population survey. Young blacks obtained a fifth of their daily calories from fast food.

These findings, from National Health and Nutrition Examination Survey (NHANES) data, were published online in a National Center for Health Statistics (NCHS) brief on February 21.

The report authors, Cheryl D. Fryar, MSPH, and R. Bethene Ervin, PhD, from the National Center for Health Statistics, from the Centers for Disease Control and Prevention, in Hyattsville, Maryland, write that previous reports showed how fast-food consumption gained momentum during the 1990s. Other studies found that those who frequently devoured fast food also tended to eat fewer healthy nutrients and gain weight.

To determine how many daily calories were obtained from fast foods, the researchers examined NHANES data from white, black, and Hispanic adults aged 20 to more than 60 years from 2007 to 2010. The respondents were stratified by income and weight.

During 2007 – 2010, fast food accounted for 11.3% of the typical American diet, down slightly from 12.8% in 2003 – 2006. The percentage of calories from fast food did not differ significantly between men (11.8%) and women (10.9%).

Consumption of fast foods dropped with age. On average, by age 60 years and older, fast food accounted for only 6.0% of the average diet, as opposed to 10.5% at age 40 to 59 years and 15.3% at age 20 to 39 years. This change in eating habits was found for both men and women.

Although among younger blacks, 21.1% of daily calories came from fast foods, among younger whites and Hispanics, only about 14.6% of daily calories were obtained from fast foods.

Similarly, among middle-aged blacks, 13.2% of calories were derived from fast foods, whereas among middle-aged whites and Hispanics, only about 10.3% of calories came from fast foods.

Seniors of all races and ethnicities had the same lower rates of fast-food consumption.

The youngest adults relied less on inexpensive takeout food as their incomes rose. Income did not affect fast-food consumption in the other 2 age groups.

Weight predicted fast-food intake. Among individuals with normal or low weight, 9.6% of calories came from noshing on fast food. However, this type of food accounted for 11.2% of calories for overweight individuals and 13.1% of calories for obese individuals. In all age groups, obese individuals derived the highest percentage of calories from fast food.

Source: NCHS data brief. Published online February 21, 2013.Article

 

Medscape Medical News © 2013  WebMD, LLC 

Race and Kidney Transplants

Race and Kidney Transplants

Time to kidney transplant varies by race, insurance

(NEW YORK) Reuters Health - Kidney disease patients who are black or lack private health insurance are less likely to get matched up with a donor organ before needing to go on dialysis, a new study suggests.

Still, researchers said, as long as patients get a kidney transplant within a year or so of starting dialysis, any extra benefit of a pre-dialysis transplant may be low.

"It's a possible benefit, but it's not entirely clear," said Dr. Morgan Grams, who led the new study at the Johns Hopkins University School of Medicine in Baltimore.

She told Reuters Health the findings represent "just another disparity" for African American patients, in particular, who take longer to get on the waitlist for a donor kidney and are less likely to get one at all.

"Studies over the last 10 to 15 years have consistently shown that minorities have poorer access to transplantation," said Dr. Douglas Scott Keith, head of the kidney transplant program at the University of Virginia Medical Center in Charlottesville.

"This article basically shows that it's persisting, it hasn't gotten much better," Keith, who wasn't involved in the new study, told Reuters Health. Grams and her colleagues looked at about 122,000 first-time kidney recipients who received their organ from a deceased donor off a transplant list between 1995 and 2011.

Nine percent of those patients had their kidney transplant before going on dialysis, and another 12 percent received a kidney within their first year on dialysis, the researchers reported Thursday in the Clinical Journal of the American Society of Nephrology.


African Americans were 56 percent less likely to receive a kidney before dialysis than whites - possibly because there was a delay in getting them on the transplant list or fewer matching donors, researchers said.

Typically, an available organ goes to the local patient who has been on the kidney transplant list the longest - but that person can be skipped if the organ is a direct match to the immune system of another patient high on the list.

People in the study who had private insurance were also three times more likely to get an early kidney than others.

Insurance is required for a transplant, so anyone with private insurance can get on the list early. Others aren't eligible for government-funded insurance until they're on dialysis.
It's still unclear whether receiving a kidney very early on improves the long-term outlook for patients with renal disease.

Pre-dialysis recipients and people who got their kidney within a year of starting dialysis were equally likely to survive for years after their transplant, the researchers found. Both did better than late-dialysis recipients.

"I would certainly not advocate postponing dialysis in the hope of getting a transplant without getting dialyzed," said Dr. Titte Srinivas, the head of transplant nephrology at the Medical University of South Carolina in Charleston, who also wasn't part of the research team. For a patient who needs it, "A short duration of dialysis is not really detrimental to health."

Srinivas told Reuters Health what's most important is for anyone diagnosed with renal failure to get on the kidney transplant list as quickly as possible. Health care reform could make that easier for some people, Grams noted, as more low-income patients will have access to insurance - and the transplant list. "People don't realize that insurance makes such a huge difference," she said.

Keith said aside from the insurance issue, researchers are still grappling with how to distribute kidneys of all different qualities, from all different types of donors, to the people who need them most.

"We should be trying to make the system as fair as possible, and to limit disparities as much as possible," he said. "The question is how to do it."

SOURCE: http://bit.ly/WUFpdl Clinical Journal of the American Society of Nephrology, online January 31, 2013 and MEDCITY News

Read more: http://medcitynews.com/2013/01/time-to-kidney-transplant-varies-by-race-insurance/#ixzz2Kbk5Tz5C

Race and Allergies

Connecting Race and Allergies

Analyzing race and ethnicity's role in allergies across the U.S.

You may be asking yourself “Why me?” as your allergies start acting up this spring. It might surprise you to know your race and ethnicity is part of the answer.

The chance of having an allergy varies dramatically based on race and ethnicity. Practice Fusion’s Research Division found that Caucasians, who have the highest rate of allergies in our data, are about 3 times more likely to have allergies than Asians, who have the lowest rate. We also found that African-Americans are about 80% more likely to have a peanut allergy than Caucasians.

Previous studies have also found a link between race and certain allergies. A recent analysis by researchers at Northwestern Medical School, for example, found a higher likelihood of sensitivity to certain foods in African-American children than in Caucasian children in a study of about 1,000 participants. We explored the relationship between race and ethnicity and common allergies in a sample of over 1.3 million medical records.

The fascinating thing about allergies is that what’s harmless for one person can be the trigger for a life-threatening allergic reaction in another. We looked at a wide range of triggers: medication, animal dander, seafood, dairy, shell fish, insect stings, soy, pollen, eggs, mold, dust and nuts. In general, the more common allergies after medications were for dairy, shell fish, pollen, dust and contact with animal dander. More unusual allergies were for nickel and baker’s yeast.

The data shows that non-Hispanics were about 66% more likely to have allergies than Hispanics. Caucasians were also much more likely to have an allergy than African-Americans or Asians.
Things get a little more mixed up, however, if you look at particular allergies. African-Americans are more allergic to peanuts than Caucasians. Caucasians are more allergic to animal dander and medication than non-Caucasians. Native Americans join them with their high chance of medication allergies.

The reason for all this variation remains unclear. Allergies are largely hereditary, but this doesn’t explain the increases in the incidence of allergies over the past 20 years. Doctors now wonder if factors related to our environment and diet actually play a larger role than previously thought. The data too could have some bias if differential reporting of allergies occurs by race.

Nevertheless, patients and doctors should be aware that these associations exist, especially for potentially serious allergies like allergies to peanuts. And hopefully more data will help us learn the underlying causes of allergies.
Source: Practice Fusion and Jake Marcus. Thanks to Barbara Showlater, M.D. and Catherine Lewis, Board Member, for letting us know about this. 

Racial link to high-risk breast cancer

African Ancestry Linked to High-Risk Breast Cancer, Study Finds

A new study finds that African ancestry is linked to triple-negative breast cancer, a more aggressive type of cancer that has fewer treatment options.

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Researchers at the University of Michigan Comprehensive Cancer Center found that, among women with breast cancer, 82 percent of African women were triple negative, 26 percent of African-Americans were and 16 percent of white Americans were.

Triple negative breast cancer is negative for three specific markers that are used to determine treatment: the estrogen receptor, the progesterone receptor and HER-2/neu.

"The most significant recent advances in breast cancer treatment have involved targeting these three receptors. But these treatments do not help women with triple-negative breast cancer.

Outcome disparities are therefore likely to increase, because fewer African-American women are candidates for these newer treatments," says study author Lisa A. Newman, M.D., M.P.H., director of the Breast Care Center at the U-M Comprehensive Cancer Center.

The study, published online in the journal Cancer, looked at 581 African American women and 1,008 white women diagnosed with breast cancer at the Henry Ford Health System in Detroit, plus 75 African women diagnosed at the Komfo Anokye Teaching Hospital in Ghana.

Researchers found that Ghanaian women were diagnosed at a younger age than American women, and with larger tumors and more advanced cancer. In addition, the Ghanaian women were more likely to test negative for each of the three markers.

Prior studies have shown that while African-American women are less likely than white women to develop breast cancer, those who are diagnosed are usually younger and are more likely to die from the disease. These characteristics, including the triple negative disease, are also more common among women with a known hereditary predisposition for breast cancer related to BRCA1 gene mutations. Other studies have also shown a hereditary breast cancer risk associated with racial-ethnic identity -- most commonly among Ashkenazi Jewish women.

"African ancestry might be associated with other links to hereditary predisposition for particular patterns of breast cancer. We hope that by studying breast cancer in African and African-American women we can identify biomarkers that might be useful for assessing risk or treating triple-negative breast cancer," says Newman, professor of surgery at the U-M Medical School.
Breast cancer statistics: 194,280 Americans will be diagnosed with breast cancer this year and 40,610 will die from the disease, according to the American Cancer Society

Additional authors: From U-M: Celina Kleer, M.D.; Valerie Takyi, M.D.; Maria Braman, M.D.; and Max Wicha, M.D.; from Henry Ford Health System: Azadeh Stark, Ph.D.; and Richard Zarbo, M.D., D.M.D.; from University of Illinois: Iman Martin, M.P.H.; from Komfo Anokye Teaching Hospital: Baffour Awuah, M.D.; Anthony Nsiah-Asare, M.D.; and Solomon E. Quayson, FWACP

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Story Source: Science Daily

The above story is reprinted from materials provided by University of Michigan Health System.

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Journal Reference:

1. Stark et al. African ancestry and higher prevalence of triple-negative breast cancer. Cancer, 2010; DOI: 10.1002/cncr.25276

Global Genome Effort and Ethnic Groups

Global Genome Effort Seeks Genetic Roots of Disease

enlarge

By decoding the genomes of more than 1,000 people whose homelands stretch from Africa and Asia to Europe and the Americas, scientists have compiled the largest and most detailed catalog yet of human genetic variation. The massive resource will help medical researchers find the genetic roots of rare and common diseases in populations worldwide. (Credit: National Human Genome Research Institute)

ScienceDaily  — By decoding the genomes of more than 1,000 people whose homelands stretch from Africa and Asia to Europe and the Americas, scientists have compiled the largest and most detailed catalog yet of human genetic variation. The massive resource will help medical researchers find the genetic roots of rare and common diseases in populations worldwide.

The 1000 Genomes Project involved some 200 scientists at Washington University School of Medicine in St. Louis and other institutions. Results detailing the DNA variations of individuals from 14 ethnic groups are published Oct. 31 in the journal Nature. Eventually, the initiative will involve 2,500 individuals from 26 populations.

"With this resource, researchers have a roadmap to search for the genetic origins of diseases in populations around the globe," says one of the study's co-principal investigators, Elaine Mardis, PhD, co-director of The Genome Institute at Washington University. "We estimate that each person carries up to several hundred rare DNA variants that could potentially contribute to disease. Now, scientists can investigate how detrimental particular rare variants are in different ethnic groups."

At the genetic level, any two people are more than 99 percent alike. But rare variants -- those that occur with a frequency of 1 percent or less in a population -- are thought to contribute to rare diseases as well as common conditions like cancer, heart disease and diabetes. Rare variants may also explain why some medications are not effective in certain people or cause side effects such as nausea, vomiting, insomnia and sometimes even heart problems or death.

Identifying rare variants across different populations is a major goal of the project. During the pilot phase of the effort, the researchers found that most rare variants differed from one population to another, and that they developed recently in human evolutionary history, after populations in Europe, Africa, Asia and the Americas diverged from a single group. The current study bears this out.

"This information is crucial and will improve our interpretation of individual genomes," says another of the study's co-principal investigators, Richard K. Wilson, PhD, director of The Genome Institute and a pioneer in cancer genome sequencing. "Now, if we want to study cancer in Mexican Americans or Japanese Americans, for example, we can do so in the context of their diverse geographic or ancestry-based genetic backgrounds."

Results of the new study are based on DNA sequencing of the following populations: Yoruba in Nigeria; Han Chinese in Beijing; Japanese in Tokyo; Utah residents with ancestry from northern and western Europe; Luhya in Kenya; people of African ancestry in the southwestern United States; Toscani in Italy; people of Mexican ancestry in Los Angeles; Southern Han Chinese in China; Iberian from Spain; British in England and Scotland; Finnish from Finland; Colombians in Columbia; and Puerto Rican in Puerto Rico.

All study participants submitted anonymous DNA samples and agreed to have their genetic data included in an online database. To catalog the variants, the researchers first sequenced the entire genome -- all the DNA -- of each individual in the study about five times. Surveying the genome in this way finds common DNA changes but misses many rare variants.
Then, to find rare variants, they repeatedly sequenced the small portion of the genome that contains genes -- about 80 times for each participant to ensure accuracy -- and they looked closely for single letter changes in the DNA sequence called SNPs (for single-nucleotide polymorphisms).

Using special tools developed to analyze and integrate the data, the researchers discovered a total of 38 million SNPs, including more than 99 percent of the variants with at frequency of at least one percent in the participants' DNA samples. They also found numerous structural variations, including 1.4 million short stretches of insertions or deletions and 14,000 large DNA deletions.

SNPs and structural variants can help explain an individual's susceptibility to disease, response to drugs or reaction to environmental factors such as air pollution or stress. Other studies have found an association between small insertions and deletions and diseases such as autism and schizophrenia.

The 1000 Genomes Project has generated massive amounts of genomic data. Simply recording the raw information took up some 180 terabytes of hard-drive space, enough to fill more than 40,000 DVDs. All of the information is freely available on the Internet through public databases.

"This tremendous resource builds on the knowledge of the Human Genome Project," says co-author George Weinstock, PhD, associate director of The Genome Institute. "Scientists and, ultimately, patients worldwide will benefit from the extensive effort to understand the shared features and geographic diversity of the human genome."

In addition to The Genome Institute, other research centers involved in the project include: the Human Genome Sequencing Center at the Baylor College of Medicine, Houston; The Broad Institute of MIT and Harvard University in Cambridge, Mass., the Wellcome Trust Sanger Institute in England; BGI Shenzhen in China; the Max Planck Institute for Molecular Genetics in Berlin; and Illumina, Inc., in San Diego.

The research is supported, in part, by a grant (U54HG3079) from the National Human Genome Research Institute at the National Institutes of Health (NIH) to The Genome Institute at Washington University in St. Louis. Other funding sources include: the Wellcome Trust; Medial Research Council; British Heart Foundation; National Basic Research Program of China; the National Natural Science Foundation of China; the Max Planck Society; Swiss National Science Foundation.
The 1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. Nature. Oct. 31, 2012
Source: Science Daily and Nature

Scientific Roots of Disease

Global Genome Effort Seeks Genetic Roots of Disease

By decoding the genomes of more than 1,000 people whose homelands stretch from Africa and Asia to Europe and the Americas, scientists have compiled the largest and most detailed catalog yet of human genetic variation. The massive resource will help medical researchers find the genetic roots of rare and common diseases in populations worldwide. (Credit: National Human Genome Research Institute)

ScienceDaily (Oct. 31, 2012) — By decoding the genomes of more than 1,000 people whose homelands stretch from Africa and Asia to Europe and the Americas, scientists have compiled the largest and most detailed catalog yet of human genetic variation. The massive resource will help medical researchers find the genetic roots of rare and common diseases in populations worldwide.

---

The 1000 Genomes Project involved some 200 scientists at Washington University School of Medicine in St. Louis and other institutions. Results detailing the DNA variations of individuals from 14 ethnic groups are published Oct. 31 in the journal Nature. Eventually, the initiative will involve 2,500 individuals from 26 populations.

"With this resource, researchers have a roadmap to search for the genetic origins of diseases in populations around the globe," says one of the study's co-principal investigators, Elaine Mardis, PhD, co-director of The Genome Institute at Washington University. "We estimate that each person carries up to several hundred rare DNA variants that could potentially contribute to disease. Now, scientists can investigate how detrimental particular rare variants are in different ethnic groups."

At the genetic level, any two people are more than 99 percent alike. But rare variants -- those that occur with a frequency of 1 percent or less in a population -- are thought to contribute to rare diseases as well as common conditions like cancer, heart disease and diabetes. Rare variants may also explain why some medications are not effective in certain people or cause side effects such as nausea, vomiting, insomnia and sometimes even heart problems or death.
Identifying rare variants across different populations is a major goal of the project.

During the pilot phase of the effort, the researchers found that most rare variants differed from one population to another, and that they developed recently in human evolutionary history, after populations in Europe, Africa, Asia and the Americas diverged from a single group. The current study bears this out.

"This information is crucial and will improve our interpretation of individual genomes," says another of the study's co-principal investigators, Richard K. Wilson, PhD, director of The Genome Institute and a pioneer in cancer genome sequencing. "Now, if we want to study cancer in Mexican Americans or Japanese Americans, for example, we can do so in the context of their diverse geographic or ancestry-based genetic backgrounds."

Results of the new study are based on DNA sequencing of the following populations: Yoruba in Nigeria; Han Chinese in Beijing; Japanese in Tokyo; Utah residents with ancestry from northern and western Europe; Luhya in Kenya; people of African ancestry in the southwestern United States; Toscani in Italy; people of Mexican ancestry in Los Angeles; Southern Han Chinese in China; Iberian from Spain; British in England and Scotland; Finnish from Finland; Colombians in Columbia; and Puerto Rican in Puerto Rico.

All study participants submitted anonymous DNA samples and agreed to have their genetic data included in an online database. To catalog the variants, the researchers first sequenced the entire genome -- all the DNA -- of each individual in the study about five times. Surveying the genome in this way finds common DNA changes but misses many rare variants.

Then, to find rare variants, they repeatedly sequenced the small portion of the genome that contains genes -- about 80 times for each participant to ensure accuracy -- and they looked closely for single letter changes in the DNA sequence called SNPs (for single-nucleotide polymorphisms).

Using special tools developed to analyze and integrate the data, the researchers discovered a total of 38 million SNPs, including more than 99 percent of the variants with at frequency of at least one percent in the participants' DNA samples. They also found numerous structural variations, including 1.4 million short stretches of insertions or deletions and 14,000 large DNA deletions.

SNPs and structural variants can help explain an individual's susceptibility to disease, response to drugs or reaction to environmental factors such as air pollution or stress. Other studies have found an association between small insertions and deletions and diseases such as autism and schizophrenia.

The 1000 Genomes Project has generated massive amounts of genomic data. Simply recording the raw information took up some 180 terabytes of hard-drive space, enough to fill more than 40,000 DVDs. All of the information is freely available on the Internet through public databases.

"This tremendous resource builds on the knowledge of the Human Genome Project," says co-author George Weinstock, PhD, associate director of The Genome Institute. "Scientists and, ultimately, patients worldwide will benefit from the extensive effort to understand the shared features and geographic diversity of the human genome."

In addition to The Genome Institute, other research centers involved in the project include: the Human Genome Sequencing Center at the Baylor College of Medicine, Houston; The Broad Institute of MIT and Harvard University in Cambridge, Mass., the Wellcome Trust Sanger Institute in England; BGI Shenzhen in China; the Max Planck Institute for Molecular Genetics in Berlin; and Illumina, Inc., in San Diego.

The research is supported, in part, by a grant (U54HG3079) from the National Human Genome Research Institute at the National Institutes of Health (NIH) to The Genome Institute at Washington University in St. Louis. Other funding sources include: the Wellcome Trust; Medial Research Council; British Heart Foundation; National Basic Research Program of China; the National Natural Science Foundation of China; the Max Planck Society; Swiss National Science Foundation.

The 1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. Nature. Oct. 31, 2012.

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Story Source:

The above story is reprinted from materials provided by Washington University in St. Louisvia Newswise.

Fatal INTERPRETATION Part IV

Fatal Interpretation Part IV: The New Biopolitics of Race and Conclusion

We have come so far in the book Fatal Invention by Dorothy Roberts that we are getting to the end—I promise. We are now at Chapter 11, “Genetic Surveillance.” Did you know the government is going to want your genetic fingerprints or does that sound a bit paranoid? Ask Dorothy Roberts who goes from violent felons to sex offenders to getting a traffic ticket. Yes, some of that is worrisome, but DNA can also be helpful. It certainly is in paternity tests on Jerry Springer’s show. Again, we are talking about policy issues, not whether race is a social construct. Unfortunately, we can’t have it both ways; use our DNA freely and totally protect our DNA.

Uh oh. Roberts says DNA is not infallible. She states, “The genetic material in government databanks has to be retrieved, transferred, transported, identified, labeled, analyzed, and stored by human hands, and there is opportunity at every stage.” I think of DNA as closely related to fingerprints and nothing horrible has happened with those. I’m not sure yet what point Roberts is trying to make. Are DNA samples better than race or what? She attacks law enforcement for being racially biased, but that’s because racism exists. Once again, another old problem with no answers or even suggestions from the author, and once again I see it as policy issues.

The last chapter is “Biological Race in a ‘Postracial’ America.” I think—finally—Roberts and I agree that the United States is not postracial at all. With arguments she makes from conservative color blindness to liberal views, she gets bogged down in her own perspective by writing things like “When racial justice advocates refer to the political meaning of race, however, it is interpreted as an expression of racism orally equivalent to forms of overt white supremacy.” Really? Or maybe we just hang out with different advocates. It takes an entire chapter to say racism is alive and thriving and to think otherwise is just ignorant, but we can’t make race go away no matter what we call it.

Roberts tries to show us ignorant people that government is evil, privatization isn’t the answer, and then she goes into a rant about the prison system, all really to no avail. She does not suggest any ways to make the system different. Anyone can complain; few do anything about it.

FINALLY, the last part of this book on page 309 is “Conclusion: The Crossroads.” Wow. Now I get it completely! Roberts contends she has proven that race is not a biological construct, and it’s not a social construct, it’s a political construct and she lights up the world with this thought. First, it’s nothing new, and has been suggested by many over the years. Second, she hasn’t proven anything. The book is disjointed and is mostly just quotes from other academics (the endnotes of quotation sources is over 50 pages long) with the author trying to tie things together while pandering to her own personal political agenda. The things she decrees…well…you just have to read them for yourselves.

My intuition and over 20 years of advocacy lead me to believe that I don’t know if there is any biological basis for race. Just when I think we really are all the same, something comes up like these:

·        Bone marrow matching is closest with someone of the same race, ethnicity, or whatever you want to call it. So, how can biology not matter?

·        The incidence of high blood pressure is higher in blacks than in any other race. So, how can biology not matter?

·        Deaths from breast cancer are highest in black women. So, how can biology not matter?

·        Asian lung cancer patients have different medical responses to tyrosine kinase inhibitors than white patients. So, how can biology not matter?

·        Diabetes is less prevalent in whites than blacks. So, how can biology not matter?

·        If you are African-American, your eGFR on lab work must be calculated differently because of a difference in muscle mass. So, how can biology not matter?

·        Asthma and bronchodilator drugs response has been shown to vary widely among racial and ethnic groups. So, how can biology not matter?

Roberts doesn’t even mention these things in her book because they don’t fit into her agenda. The danger is that some people believe what Roberts has implied, for example that there is no reason for racially/genetically bone marrow donors for multiracial people. She has not said that, but is guilty by implication and omission and has caused more people than she knows to state that “Dorothy Roberts has found that multiracial people do not have to enlarge the bone marrow donor pool.” It’s just not true. Please read this book carefully and do your own research into what other top medical specialists, think. Look at the clinical studies and research.

The truth is closer to this: we do not know with absolute certainty if race has any biological basis. It really doesn’t matter what kind of construct race is or what we call it, it’s still here, it’s still a problem, and no one knows how to fix it. Roberts rehashing of old problems is not going to help. She is a civil rights professor, and she could really be useful in helping with answers to things like why we’ve been told that multiracial people have no legal standing because they are not a protected group under the law. She would know what to tell the multiracial engineer who was hired as black and fired as white.

I think Dorothy Roberts set out to write an academic tome attacking the pharmaceutical industry, specifically BiDil. However, she never does reveal the other side of the story, and she succeeded best in that. The bigger problem is that certain people began misinterpreting the book, raving that this book solves all the racial problems and must be read because the author proves—finally!—that race does not exist or if it does, it’s not biological at all. The problem is bigger because if we drop “race” out of things like clinical trials and medical testing, people could be hurt and possibly even die.

Race has bred racism; I think we can all agree on that. Rather than spending time on what word(s) to change “race” to, such as “political construct,” can’t we work on educating policy makers? It’s going to take academics like Roberts and advocates like me and the members of Project RACE to make certain that those who make the policies know and understand what’s at stake and how people are similar and different. Isn’t that what diversity is about? We have tackled important issues with policymakers like the need for self-identification, for multiracial people to have a choice, and that no one should be invisible in the healthcare system of this country.

That 0.1 percent difference is actually huge. I think race-based medicine is definitely a dilemma and certainly one I can’t solve, neither can Roberts. Truly personalized medicine could happen with the help of The Human Genome and DNA; wouldn’t it be a tragedy if we never get there because we stop potential medical progress because we are afraid of what we might find out along the way? It could indeed be a fatal invention.

Fatal Multiracial? The Multiracial Advocacy

Fatal Interpretation Part I: Believing in Race in the Genomic Age

I heard about a book called Fatal Invention by Dorothy Roberts and didn’t think much about it. I knew the book was about the age old debate on whether race is a biological or social construct, and that there are hundreds, if not thousands of articles taking either side. Ho Hum. I did not plan to read it.

Then people started talking and typing about how this book changed their lives. How Roberts totally debunks and proves race is now a political construct. Proof?! This I had to read.

I am not a medical doctor, social scientist, politician, or anthropologist, and to be fair, neither is Dorothy Roberts. She is an academic. What really tipped me over the edge was an incident in which a very intelligent person—in my judgment—told me she wished she had never become a bone marrow donor thinking she was potentially helping critically ill multiracial people, and then learned from this book that was incorrect. I was stunned. I bought the book.

I began to read the book and decided to review it with an open mind. If Roberts does in fact make racial classifications, or whatever she chooses to call them, go away, then I might be able to jump on her bandwagon. That would be a good thing.  We could all just be humans and races would be non-existent. I have stated from the very beginning of Project RACE that multiracial people should be able to have the option of designating themselves as multiracial as long as there are racial classifications. I have also said I don’t believe that will happen in my lifetime or in my children’s lifetimes, I would be thrilled to be wrong.

I have also decided to interpret Roberts without falling into academic, scientific, mathematic, or anthropologic speak that she uses. I’ll try my best to break it down into things most of us understand and not use footnotes. This is my review, not my book.

The best way to review this book in sections, following the structure of the book, because I doubt many of the people who bought it actually made it past Part I, maybe Part II. I was eager to read everything Dorothy Roberts had to say.

Roberts writes a lot about race being a “political system.” When everyday people think about politics, it usually is thought of as the way we choose government officials and often stretches to decisions about policy. There are many other various definitions. Roberts never really tells the reader what her definition of “political” is, but I can give her the benefit of the doubt and assume she is not writing about the upcoming elections, but rather anything government does on behalf of the general public.

The overall first portion of the book tries to answer such questions as “Where does Race Come From?” Roberts is pretty much all over the place, from definitions to subjugation to slavery to a one-liner on interracial marriage. Suddenly, it pops up that there is no biological test for whiteness and she writes, “White means belonging to the group of people who are entitled to claim white privilege.” I couldn’t find that definition in any dictionary, but I did learn that white is also a word for the drug cocaine.

Then Roberts gets to the census and how different changes have been made in racial categories from 1790 to 2010. That’s when I started to wonder about the “facts” in this book. She makes her case in three pages that the census is responsible for misleading us all into believing in race, and everything they do is bad. I’m no fan of the US Census Bureau, but they did not create what we know as race, they just put them into categories. She also lets readers know that her birth certificate states “Mother—Negro; Father—white.” She apparently blames society for the reason she was as she says in her own words, “born a Negro,” even though her birth certificate did not state a race for her.

But enough about the author. Next we get into Chapter 2, Separating Racial Science from Racism. Enter the Human Genome Project, which determined that human beings are genetically 99.9 per cent the same with 0.1 percent of human genetic difference. Now Roberts goes into how scientists created a racial order.

Again, Roberts quotes academics quoting academics, but mostly ones that agree with her. For the most part of this section, the arguments are old, but Roberts does a good job with the history of race. If you want a good read about DNA, this part could be for you. So now we have Roberts defending that the 0.1 percent human genetic differences are meaningful, but that does not mean race should be organized by the difference. Point taken, but then she drops the ball by throwing around other possibilities. That’s where it ends. Stay tuned for Part II. 

New Diabetes Study

Study Reveals Extent of Type 2 Diabetes Problem in Black and Minority Ethnic Populations

13-Sep-2012

September 2012 - Half of all people of South Asian, African and African Caribbean descent will develop diabetes by age 80 according to a new study. The study is the first to reveal the full extent of ethnic differences in the risk of developing type 2 diabetes and also provides answers as to the causes of the increased risk.

The findings come from the Southall and Brent REvisited (SABRE) study, a large-scale population based study funded by the Wellcome Trust and British Heart Foundation which has followed nearly 5000 middle-aged Londoners of European, South Asian, African and African Caribbean descent for over 20 years.

Type 2 diabetes is a long term condition that affects approximately 2.9 million people in the UK. In total, an estimated $11.9 billion is spent each year on treating type 2 diabetes and its complications. Early diagnosis and careful management are vital in order to prevent complications such as heart attack, stroke and kidney disease.

It has been known for some time that people of South Asian, African and African Caribbean descent are at increased risk of developing diabetes in mid-life, but it is not known why this is or whether this extra risk continues as people get older. By tracking the development of diabetes in the SABRE cohort, researchers led by Nish Chaturvedi at Imperial College London have revealed the extent of the problem in the UK and offer some explanations as to why these differences arise.

The study reveals that by age 80, twice as many British South Asian, African and African Caribbean men and women had developed diabetes compared with Europeans of the same age. Approximately half of all South Asians, Africans and African Caribbeans in the UK will develop the disease by age 80 compared with only one in five of European descent.

The study looked at individuals who did not already have type 2 diabetes at the start of the study, which began following participants aged 40 to 69 from 1988 onwards, and recorded those that developed the disease. The team found that while African, African Caribbeans and Europeans tend to be diagnosed at around the same age, 66-67 years, South Asian men were 5 years younger on average when diabetes was diagnosed, meaning that they are at even greater risk of complications.

In order to understand the causes of this increased diabetes risk, the researchers looked at a number of risk factors across the different ethnic groups.

Family history of diabetes is known to be an important risk factor for all ethnic groups. However, even though over half of South Asian, African and African Caribbean men and one third of women had a family history of diabetes, this did not explain the extra risk over their European counterparts.

It is known that the onset of type 2 diabetes is frequently preceded by an increase in insulin resistance, where the body becomes insensitive to the effects of insulin on glucose metabolism, resulting in high circulating glucose. Weight gain and obesity are known factors that can underlie increases in insulin resistance.

The team found that carrying fat around the trunk or middle of the body in mid-life together with increased resistance to the effects of insulin explained why South Asian, African and African Caribbean women are more at risk of developing diabetes than British European women. However, this explained only part of the increased risk in South Asian, African and African Caribbean men, suggesting that other factors that are as yet unknown may also play a part.
The findings are published in the journal Diabetes Care.

Dr Therese Tillin, from the National Heart and Lung Institute at Imperial College London, said "Not only does this study increase our understanding of the reasons for ethnic differences in risks of diabetes, it highlights the astonishingly high risk of diabetes in middle-aged people in our ethnic minorities and the importance of early diagnosis and careful management. Future analyses will examine methods of predicting which individuals are most risk of diabetes– the good news is that diabetes can be prevented if the warning signs are recognised early enough."

Professor Nish Chaturvedi, also from the National Heart and Lung Institute at Imperial College London, said: "We set up the SABRE study in 1988 and it is one of the largest and longest running tri-ethnic cohorts in the UK. We are enormously grateful to all the participants for their continuing support of the study, which has enabled us to begin to understand why diabetes happens in some people and not in others. We plan to extend our research to examine the roles of genes and the environment at different stages of life in causing diabetes in the three ethnic groups."

Dr Hélène Wilson, Research Advisor at the British Heart Foundation (BHF), said: "This study suggests the higher rate of diabetes – a major risk factor for heart attacks and strokes – in some South Asian and African Caribbean women is due to increased levels of obesity, particularly the build-up of fat around the waist, and higher resistance to insulin, which helps the body process sugar.

"This is a very encouraging discovery because it underlines the fact that controlling your weight by eating well and getting active can have a significant protective effect on your health. There"s a wealth of existing evidence that keeping the weight off by eating a healthy balanced diet and being physically active will reduce your risk of heart disease and type 2 diabetes, whatever your ethnic group."

Professor Danny Altman, Head of Pathogens, Immunology and Population Health at the Wellcome Trust, said: "Chronic diseases such as diabetes are a growing threat to global health as people are not only living longer lives but also begin to develop disease at a younger age.

Long-term population studies like the SABRE study are essential for helping us to understand the factors that contribute to disease and to identify the communities that are most at risk."
SABRE is funded at follow-up by the Wellcome Trust and British Heart Foundation. The baseline studies were funded by the Medical Research Council, British Heart Foundation and Diabetes UK.
Source: Diabetes News

Diabetes and Ethnicity Study: The Multiracial Advocacy

 

Hispanics May Face Higher Risk for Type 2 Diabetes: Study

Differences seen in how the pancreas responds to excess fat with insulin

WEDNESDAY, Sept. 12 (HealthDay News) -- Hispanics are more likely to store fat in their pancreas, but less likely to be able to produce more insulin to compensate for this excess fat, putting them at higher risk for type 2 diabetes, a new study suggests.

Insulin is a hormone that helps regulate metabolism. People with insulin resistance still produce insulin but their bodies don't use it correctly. It can be a forerunner for type 2 diabetes.

"Not all people who are overweight or obese and who have insulin resistance go on to develop diabetes," Richard Bergman, director of the Cedars-Sinai Diabetes and Obesity Research Institute in Los Angeles, and study lead author, said in a Cedars-Sinai news release. "If we can determine who is most likely to develop diabetes and why, then we can make strides toward preventing it in those individuals."

In conducting the study, the researchers used a noninvasive medical imaging technique, known as magnetic resonance spectroscopy, to measure the amount of fat in the organs of white, black and Hispanic participants. All of the people involved in the study were equally overweight and shared many of the symptoms of prediabetes.

Participants also took an oral glucose tolerance test and intravenous glucose tolerance test to determine their insulin resistance.

"One of the reasons some people are at increased risk, we believe, is that fatty pancreas is unable to secrete enough insulin, which results in an individual progressing from impaired glucose tolerance to type 2 diabetes," Lidia Szczepaniak, director of magnetic resonance spectroscopy at the Cedars-Sinai Heart Institute and Biomedical Imaging Research Institute, said in the release. "In our study, we found Latinos were especially vulnerable, as they tended to store more fat in the pancreas and their compensatory insulin secretion was entirely suppressed."

Diabetes affects nearly 26 million Americans and another 79 million are prediabetic, according to the U.S. Centers for Disease Control and Prevention. The disease is the seventh-leading cause of death in the United States and a major cause of heart disease and stroke.
The study was published online Sept. 11 in Diabetes Care.

While the study found an association between ethnicity and insulin resistance, it did not prove a cause-and-effect relationship.
Content by:

SOURCE: Cedars-Sinai, news release, Sept. 11, 2012

 

More Race in Medicine: The Multiracial Advocacy

The Ethnic Gap in Diabetes The risk of diabetes may be different for people from different racial and ethnic backgrounds....  But when does this gap begin? Findings from a recent study showed that ethnic differences in diabetes risk can be spotted even before people develop full-blown diabetes. The authors concluded, "Ethnic differences can be detected at both the early and later stages of the diabetes disease process." Carlos Lorenzo, MD, and his colleagues from the University of Texas Health Science Center wanted to see if ethnic differences in diabetes risk started early in the diabetes disease process. Dr. Lorenzo and colleagues compared the risks of impaired glucose tolerance, impaired fasting glucose and diabetes between Mexican Americans and non-Hispanic whites. They found that Mexican Americans were 1.48 times more likely to have impaired glucose tolerance and 1.71 times more likely to have impaired fasting glucose, compared to whites. In addition, Mexican Americans were 2.20 times more likely than whites to develop diabetes, even among participants who started the study with normal 2-hour glucose (a measure of blood sugar levels 2 hours after eating a glucose load). Obesity also played a role in the relationship between ethnicity and the risk of developing impaired glucose tolerance or diabetes. Among non-obese participants, Mexican Americans had a higher risk of impaired glucose tolerance or diabetes. Among obese participants, however, these risks were similar between Mexican Americans and whites. Even though whites generally had a lower risk of prediabetes and diabetes, their risk became similar to that of Mexican Americans when they became obese This study included 3,015 Mexican Americans and non-Hispanic whites between 25 and 64 years of age. Source: Diabetes Care, Aug. 24, 2012